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Toxicological evaluations in macrophages and mice acutely and chronically exposed to halloysite clay nanotubes functionalized with polystyrene
Yanis Toledano-Magaña
LETICIA FLORES SANTOS
GEORGINA MONTES DE OCA RAMIREZ
ALFONSO GONZALEZ MONTIEL
Juan Carlos Garcia_Ramos
Conchi Mora
Noemi Alejandra Saavedra_Avila
Luisa Carolina Gonzalez Ramirez
Juan P Laclette
Julio Carrero
Acceso Abierto
Atribución-NoComercial-CompartirIgual
2470-1343
https://pubs.acs.org/doi/10.1021/acsomega.1c04367
https://pubs.acs.org/doi/10.1021/acsomega.1c04367
https://pubs.acs.org/toc/acsodf/6/44
Immunology
Anatomy
Halloysite clay nanotubes (HNTs) have been proposed as highly biocompatible for several biomedical applications. Various polymers have been used to functionalize HNTs, but scarce information exists about polystyrene for this purpose. This work evaluated polystyrene-functionalized HNTs (FHNTs) by comparing its effects with non-FHNTs and innocuous talc powder on in vitro and in vivo models. Monocyte-derived human or murine macrophages and the RAW 264.7 cell line were treated with 0.01, 0.1, 1, and 100 μgmL−1 FHNTs, HNTs, or talc to evaluate the cytotoxic and cytokine response. Our results show that nanoclays did not cause cytotoxic damage to macrophages. Only the 100 μg mL−1 concentration induced slight proinflammatory cytokine production at short exposure, followed by an anti-inflammatory response that increases over time. CD1 mice treated with a single dose of 1, 2.5, or 5 mg Kg−1 of FHNTs or HNTs by oral and inhalation routes caused aluminum accumulation in the kidneys and lungs, without bodily signs of distress or histopathological changes in any treated mice, evaluated at 48 h and 30 days post-treatment. Nanoclay administration simultaneously by four different parenteral routes (20 mg Kg−1) or the combination of administration routes (parenteral + oral or parenteral + inhalation; 25 mg Kg−1) showed accumulation on the injection site and slight surrounding inflammation 30 days post-treatment. CD1 mice chronically exposed to HNTs or FHNTs in the bedding material (ca 1 mg) throughout the parental generation and two successive inbred generations for 8 months did not cause any inflammatory process or damage to the abdominal organs and the reproductive system of the mice of any of the generations, did not affect the number of newborn mice and their survival, and did not induce congenital malformations in the offspring. FHNTs showed a slightly less effect than HNTs in all experiments, suggesting that functionalization makes them less cytotoxic. Doses of up to 25 mg Kg−1 by different administration routes and permanent exposure to 1 mg of HNTs or FHNTs for 8 months seem safe for CD1 mice. Our in vivo and in vitro results indicate that nanoclays are highly biocompatible, supporting their possible safe use for future biomedical and general-purpose applications.
También es autor: Marco Gudiño Zayas (UNAM. F. Medicina)
The authors thank the financial support of Centro de Investigación y Desarrollo S.A. de C.V., MACRO-M, UABCPTC-869 grant 511-6/2020-8608 (YTM), UABC-PTC-819 grant 511-6/2020-8608 (JCGR), Consejo Nacional de Ciencia y Tecnología CONACyT-284830 (JCC), PAPIIT-UNAMIN206316 (JCC), and Spanish Ministerio de Ciencia y Tecnología Grant SAF2008-02536. The authors thank Pavel Petrosyan and Mariamne Dehonor Gomez for the technical assistance to this work.
Conceptualization, Y.T.-M., L.F.-S., A.G.-M., and G.M.deO.; data curation, Y.T-M., J.C.G.-R., N.-A.S.-A., and J.C.C.; formal analysis, Y.T-M., J.C.G.-R., N.-A.S.-A., L.-C.G.-R., J.P.L., and J.C.C.; funding acquisition, Y.T.-M., L.F.-S., A.G.-M. J.C.G.-R, C.M., and J.C.C; investigation, Y.T-M., J.C.G.-R., G.M.deO., and M.G.Z.; methodology, Y.T.-M., C.M., N.A.S.-A., J.P.L., and J.C.C.; project administration, Y.T.-M., L.F.-S., A.G.-M., G.M.deO., J.C.G.-R., C.M., and J.C.C.; resources, L.F.-S., A.G.-M., G.M.deO., J.C.G.-R., C.M., J.P.L., and J.C.C.; supervision, L.F.-S., A.G.-M., C.M., J.P.L., and J.C.C.; validation, Y.T-M., J.C.G.-R., and N.A.S.-A.; visualization, Y.T-M., J.C.G.-R., N.A.S.-A.; M.G.-Z., and L.C.G.-R.; writing original draft, Y.T.-M. and J.C.G.-R.; and writing review and editing, all authors contributed. All authors have read and agreed to the published version of the manuscript.
Notes: The authors declare no competing financial interest.
American Chemical Society
2021
Artículo
ACS Omega, vol. 9, no. 6, pág. 29882-29892
Inglés
Público en general
Toledano-Magaña, Y., Flores-Santos, L., Montes de Oca, G., González-Montiel, A., García-Ramos, J.-C., Mora, C., Saavedra-Ávila, N.-A., Gudiño-Zayas, M., González-Ramírez, L.-C., Laclette, J. P., & Carrero, J. C. (2021). Toxicological evaluations in macrophages and mice acutely and chronically exposed to halloysite clay nanotubes functionalized with polystyrene. ACS Omega, 6(44), 29882-29892. https://doi.org/10.1021/acsomega.1c04367
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